Mayatepek E, Lehmann W D, Fauler J, Tsikas D, Frölich J C, Schutgens R B, Wanders R J, Keppler D
German Cancer Research Center, Heidelberg.
J Clin Invest. 1993 Mar;91(3):881-8. doi: 10.1172/JCI116309.
The degradation of leukotrienes by beta-oxidation from the omega-end proceeds in peroxisomes (Jedlitschky et al. J. Biol. Chem. 1991. 266:24763-24772). Peroxisomal degradation of leukotrienes was studied in humans by analyses of endogenous leukotrienes in urines from eight patients with biochemically established peroxisome deficiency disorder and eight age- and sex-matched healthy infant controls. Leukotriene metabolites were separated by high-performance liquid chromatography, quantified by radioimmunoassays, and identified as well as quantified by gas chromatography-mass spectrometry. Urinary leukotriene E4 (LTE4) and N-acetyl-LTE4 excretions, relative to creatinine, were increased > 10-fold in the patients in comparison to healthy infants. The beta-oxidation product omega-carboxy-tetranor-LTE3 averaged 0.05 mumol/mol creatinine in the controls but was not detectable in the patients. However, omega-carboxy-LTE4 (median 13.6 mumol/mol creatinine) was significantly increased in the patients' urine, whereas LTB4 (median 0.07 mumol/mol creatinine) and omega-carboxy-LTB4 were detected exclusively in the urines of the patients. These data indicate an impairment of the inactivation and degradation of both LTE4 and LTB4 in patients with peroxisomal deficiency. The increased levels of the biologically active, proinflammatory mediators LTE4 and LTB4 might be of pathophysiological significance in peroxisome deficiency disorders. This is the first and so far only condition with a pronounced urinary excretion of omega-carboxy-LTE4, omega-carboxy-LTB4, and LTB4. This impaired catabolism of leukotrienes and the altered pattern of metabolites may be of diagnostic value. These findings underline the essential role of peroxisomes in the catabolism of leukotrienes in humans.
白三烯通过从ω端进行β氧化在过氧化物酶体中降解（杰利茨基等人，《生物化学杂志》，1991年。266:24763 - 24772）。通过分析8名经生化确诊患有过氧化物酶体缺乏症的患者以及8名年龄和性别匹配的健康婴儿对照的尿液中的内源性白三烯，对人类白三烯的过氧化物酶体降解进行了研究。白三烯代谢产物通过高效液相色谱法分离，通过放射免疫测定法定量，并通过气相色谱 - 质谱法进行鉴定和定量。与健康婴儿相比，患者尿液中白三烯E4（LTE4）和N - 乙酰 - LTE4相对于肌酐的排泄量增加了10倍以上。β氧化产物ω - 羧基 - 四降 - LTE3在对照组中平均为0.05μmol/mol肌酐，但在患者中未检测到。然而，ω - 羧基 - LTE4（中位数为13.6μmol/mol肌酐）在患者尿液中显著增加，而LTB4（中位数为0.07μmol/mol肌酐）和ω - 羧基 - LTB4仅在患者尿液中检测到。这些数据表明过氧化物酶体缺乏症患者中LTE4和LTB4的失活和降解受损。具有生物活性的促炎介质LTE4和LTB4水平升高可能在过氧化物酶体缺乏症中具有病理生理学意义。这是迄今为止第一个也是唯一一个ω - 羧基 - LTE4﹑ω - 羧基 - LTB4和LTB4在尿液中大量排泄的情况。白三烯这种受损的分解代谢以及代谢产物模式的改变可能具有诊断价值。这些发现强调了过氧化物酶体在人类白三烯分解代谢中的重要作用。
